No Improvement in Stone Expulsion Rate in Patients with Renal Colic Treated with Tamsulosin

Results of a multicenter, randomized, double-blind trial [Arch Intern Med. 2010;170 (22):2021-2027] show that the adrenergic alpha-blocker tamsulosin did not accelerate the expulsion of distal ureteral stones in patients with renal colic. Although a number of published studies have suggested that medical expulsive therapy can facilitate urinary stone passage in patients with renal colic, more recent studies have reported negative results with beta-blockers. All of these studies, however, have been criticized for their methodologic flaws, which include short follow-up, small sample sizes, and inconsistencies such as variable definitions of stone sizes and stone-free state. Because of this, the joint European Association of Urology-American Urological Association Nephrolithiasis Guideline Panel, among others, has advocated for the need of high-quality, double-blind, randomized controlled trials on expulsion therapies to improve the quality of the research on this topic. To this end, investigators for the European Tamsulosin Study Group conducted the current study to evaluate the efficacy and safety of tamsulosin hydrochloride in patients with ureteral colic due to a distal ureteral stone. The study included 129 patients with acute renal colic recruited from emergency wards in 6 French hospitals between February 2002 and December 2006. Patients included in the study were >18 years of age, had a radio-opaque, distal ureteral stone between 2 and 7 mm in diameter, and agreed to be followed for 6 weeks. Patients were excluded if they were pregnant or breastfeeding, were receiving an alpha- or beta-blocker, had transient hypotension or liver impairment, or required a surgical procedure due to infection or pain after medical treatment. After initial treatment with intravenous ketoprofen (50 mg) and phloroglucinol (80 mg), the 129 patients were randomized to further treatment with oral ketoprofen and phloroglucinol for 5 days and tamsulosin (0.4 mg) (n=66) or matching placebo (n=63). Of these 129 patients, 61 patients in each treatment group were included in the analysis. Based on the primary end point of the study, which was time to stone expulsion between study inclusion and day 42, no difference between the 2 treatment groups was found. The estimated hazard ratio based on the comparison of the time to stone expulsion between randomization and day 42 in the placebo and tamsulosin groups was 1.27 (95% confidence interval, 0.81-2.04; P=.30). Analysis of secondary end points also indicated no difference between the placebo and tamsulosin groups in the number of patients with spontaneous expulsion of stones within the 42 days of the study (70.5% vs 77.0%, respectively; P=.41), or in the average time to stone passage (10.1 vs 9.6 days; P=.82). In addition, no difference was seen in the number of patients given placebo or tamsulosin who experienced a relapse in pain during follow-up (59.3% vs 46.7%, respectively; P=.17) or who required morphine (11.5% vs 6.6%; P=.34). According to the authors, these results, which show no difference with tamsulosin versus placebo and are contrary to previously published results, highlight several methodologic aspects of the study, including the large sample size and high power that allowed for detection of small benefits. The study also included the systematic use in both groups of nonsteroidal anti-inflammatory drugs, which, the authors emphasize, are highly effective in relieving symptoms of acute renal colic. The authors also emphasize that the study included patients who are commonly encountered in emergency departments in Western countries; therefore, the results are transferable to populations in these countries. According to the authors, “this is all the more important to consider because the current American and European guidelines recommend the use of medical expulsive therapy using alpha-blocking drugs without any restriction concerning the size of stones smaller than 10 mm.”